Open Label NK Cell Infusion (FATE-NK100) With Subq IL-2 in Adults With AML

Inclusion Criteria:

- ≥18 but ≤ 70 years of age

- Diagnosis of acute myeloid leukemia (AML) and meets one of the following disease
criteria:

* Primary induction failure:

** De Novo AML: no CR after 2, 3 or 4 induction attempts with high dose chemotherapy

- Secondary AML (from MDS or treatment related): no CR after 1, 2 or 3 cycles of
high dose chemotherapy

- Relapsed:

- Not in CR after 1 or 2 cycles of standard re-induction therapy

- Relapse diagnosed at the time of the 6 months post-HCT standard of care follow-up
or later (i.e. based on bone marrow biopsy performed Day +170 or later) and
without evidence of graft versus host disease (GVHD)

- For patients > 60 years of age, the minimum of 1 cycle of standard
chemotherapy is not required.

- Available HLA-matched or better but not fully HLA-matched (2/4 or 3/4 antigens)
related donor (aged 18 to 75 years) with donor/recipient match based on a minimum of
intermediate resolution DNA based Class I typing of the A and B locus who is CMV
seropositive.

- Karnofsky Performance Status ≥ 60%

- Adequate organ function within 14 days of study registration (28 days for pulmonary
and cardiac) defined as:

- Creatinine: Estimated glomerular filtration rate (eGFR) ≥ 50 mL/min/1.73m^2 per
current institutional calculation formula

- Hepatic: AST and ALT ≤ 3 x upper limit of institutional normal

- Pulmonary Function: oxygen saturation ≥ 90% on room air; PFT's required only if
symptomatic or prior known impairment - must have pulmonary function >50%
corrected DLCO and FEV1

- Cardiac Function: LVEF ≥ 40% by echocardiography or MUGA

- No symptomatic active conduction system abnormalities

- Able to be off prednisone or other immunosuppressive medications for at least 3 days
prior to FATE-NK100 cell infusion (excluding preparative regimen premedications)

- Sexually active females of child bearing potential and males with partners of child
bearing potential must agree to use effective contraception during therapy and for 4
months after completion of therapy

- Voluntary written consent prior to the performance of any research related procedures

Arm Specific Inclusion Criteria

High-Risk aGVHD (ARM 1):

- Pediatric or adult (ages 0-76 years) HCT recipients with high-risk acute GVHD, as
determined either by the refined MN acute GVHD risk score [28]:
http://z.umn.edu/MNAcuteGVHDRiskScore OR high risk on the basis of blood biomarkers (Ann
Arbor Score 3) [31]. Patients in this arm must start treatment within the first 7 days
after onset of high-risk aGVHD.

or

Steroid- Dependent aGVHD (ARM 2A):

- Pediatric or adult (ages 0-76 years) HCT recipient with grade II-IV steroid-dependent
acute GVHD, defined as any one of the following: Flare of acute GVHD of at least grade
II/IV severity within 8 weeks of tapering down or (off of) immunosuppression for acute
GVHD, with the flare occurring on ≤0.5 mg/kg prednisone. This can include late-onset aGVHD
and overlap syndrome.

or

Steroid-Refractory aGVHD (ARM 2B):

- Pediatric or adult (ages 0-76 years) HCT recipient with grade II-IV steroid refractory
acute GVHD, defined as any one of the following:

- No response of acute GVHD after at least 4 days of systemic corticosteroids of at
least 2 mg/kg prednisone or equivalent

- Progression of acute GVHD within 3 days of systemic corticosteroids of at least 2
mg/kg prednisone or equivalent

- Failure to improve to at least grade II acute GVHD after 14 days of systemic
corticosteroids, with initial doses of at least 2 mg/kg prednisone or equivalent

- Flare of acute GVHD of at least grade II/IV severity while on steroids at a dose
>0.5/mg/kg/day. This can include late-onset aGVHD and overlap syndrome.

Exclusion Criteria:

- Myocardial Infraction (MI) within the previous 6 months

- Acute leukemias of ambiguous lineage

- Pregnant or breastfeeding - The agents used in this study include those that fall
under Pregnancy Category D - have known teratogenic potential. Women of child bearing
potential must have a negative pregnancy test at screening

- History of or known active CNS involvement with AML

- Active autoimmune disease requiring systemic immunosuppressive therapy

- History of severe asthma and currently on chronic systemic medications (mild asthma
requiring inhaled steroids only is eligible)

- New or progressive pulmonary infiltrates on screening chest X-ray or chest CT scan
unless cleared for study by Pulmonary. Infiltrates attributed to infection must be
stable/improving (with associated clinical improvement) after 1 week of appropriate
therapy (4 weeks for presumed or documented fungal infections).

- Uncontrolled bacterial, fungal or viral infections including HIV-1/2 or active
hepatitis C/B - chronic asymptomatic viral hepatitis is allowed

- Received any investigational agent within the 14 days before the start of study
treatment (1st dose of fludarabine)